Strategies for the synthesis of novel glycoconjugates

Abstract

A chemical reaction wherein two individual molecules are coupled together covalently in the presence or absence of reagents is known as a conjugation reaction and if the reacting partners are biomolecules then it is known as bioconjugation If the two reacting partners are saccharide and nucleobase then the conjugate is called as nucleoside and if a conjugate is prepared from two saccharides then it can be termed as disaccharide Conjugation of molecules is important for studying various cellular events such as interactions between them imaging of cells for the measurement of distances between epitopes for modification of materials etc Amidation Native Chemical Ligation Staudinger ligation azide alkyne involved 3 2 cycloaddition 8216 click 8217 reaction olefin metathesis imine formation tetrazine based ligation Michael addition are some of the bioconjugation methods among these Staudinger ligation tetrazine based ligation and click reaction are the most popular and bioorthogonal conjugations In my thesis entitled Strategies for the Synthesis of Novel Glycoconjugates we showed that various pseudo saccharide conjugates such as pyrimidine nucleosides thiosaccharides and thiotrehaloses can be synthesized by utilizing concepts from gold catalyzed glycosylation repertoire on designer mono saccharide building blocks Most of the above methods and the one that I delineated above are useful to study binary complexes as only two partners participate in the conjugation In contrast methods for multi and poly valent display of single molecule exploiting dendrimers nanoparticles calixarenes etc as templates are known However stepwise conjugation of molecules to get ternary complexes in a modular fashion is still challenging In my next attempt we have successfully utilized dichlorotetrazine as a template for the synthesis of ternary conjugates in a modular fashion exploiting SNAr and Inverse Electron Demand Diels Alder reactions We have successfully synthesized a ternary conjugate that has fucp manp and galp residues